Molecular and qualitative characterization of compatibility between valacyclovir hydrochloride and excipients as raw materials for the development of solid oral dosage formulation

The objective of this present study is to know the compatibility of valacyclovir hydrochloride (VCH) with common excipients that would be utilized to develop solid oral dosage forms. Several spectroscopy techniques were used to know the possible interactions of VCH with excipients. More, a molecular docking study was also carried out to see the interaction of VCH with excipients. In vitro study of a physical mixture of VCH with excipients was executed to know the release of a drug. Several analytical techniques such as differential scanning calorimetry, nuclear magnetic resonance spectrometer, and Fourier-transform infrared (FTIR) spectroscopy have been utilized to know the drug-excipient compatibility. Further, possible interactions between valacyclovir and different excipients were assessed by thin-layer chromatography. In vitro dissolution studies in different sets of experiments were done to determine the influence of the hydrophobic and hydrophilic nature of excipients (on the dissolution profile of VCH using USP II-type dissolving apparatus). Moreover, in silico molecular docking studies were also done to know any possible molecular interactions among drugs and excipients using AutoDock VINA 1.2.0 software and GROMACS 5.0 software. FTIR and 1H NMR spectra of VCH and physical mixtures of VCH and excipients were compared and it was observed that no significant deviation of characteristic peaks in infrared spectroscopy and 1H NMR signals was detected. The endothermic peak of VCH in the physical mixtures of drugs and excipients was found in approximately the same position. In vitro dissolution studies displayed the influence of the hydrophobic and hydrophilic nature of excipients on the dissolution profile of VCH. For the physical mixture of VCH with lactose (LAC) and dicalcium phosphate (DP), % drug release was found to be 31.96% and 33.16% at 10 min, whereas the amount of % drug released for the mixture of VCH and talc was 25.00%. For two other excipients such as LAC and DP, the % drug release was determined to be 42.96% and 41.64%, respectively, for 30 min. The docking study also provided insights into the lowest energy conformations. Docking study anticipated that the number of interactions were more between valacyclovir and LAC (four nos.) in comparison to valacyclovir and microcrystalline cellulose (MCC) (two nos.). This interaction showed that in vitro drug release for the physical mixture of VCH with MCC was higher than a mixture of valacyclovir with LAC. A compatibility study of VCH by analytical techniques established that VCH was compatible with utilized excipients. Drug dissolution of VCH and physical mixture of MCC exhibited the maximum amount of drug release whereas a mixture of VCH with magnesium stearate released the minimum amount of drug for both short (10 min.) and long (30 min.) period. Docking studies disclosed that the LAC complex showed less deviation with less root mean square deviation value in comparison to the microcrystalline complex. Thus, the LAC complex has more hydrogen bonds and it was more stable as compared with the MCC complex. Therefore, VCH and used excipients could be used for solid dose formulations.